Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years — IVY Network, 20 U.S. States, February 2022–May 2023

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.


Introduction
Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of severe respiratory disease in * These authors contributed equally to this report.older adults.In the United States, an estimated 60,000-160,000 RSV-associated hospitalizations and 6,000-10,000 RSV-associated deaths occur each year among adults aged ≥65 years (1).On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended RSV vaccination for adults aged ≥60 years using shared clinical decision-making † (1).Understanding the severity of RSV disease compared with that of other respiratory viral diseases in older adults is needed to guide this shared patient-provider clinical decision-making.

Methods
During February 1, 2022-May 31, 2023, adults aged ≥60 years with acute respiratory illness § and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection who were admitted to any of 25 hospitals in 20 U.S. states participating in the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network ¶ were eligible for inclusion in this analysis.Demographic and clinical data were obtained from patient or proxy interview and medical records, including in-hospital outcomes observed by day 28 of hospitalization.Upper respiratory specimens were collected from enrolled patients near the time of admission and tested at a central laboratory (Vanderbilt University Medical Center, Nashville, Tennessee) † Unlike age-and risk-based recommendations, for which the default decision should be to vaccinate the patient unless vaccination is contraindicated, shared clinical decision-making recommendations have no default.The decision whether to vaccinate may take into account the best available evidence regarding who would benefit from vaccination; the individual patient's characteristics, values, and preferences; the vaccine characteristics; and the clinician's discretion.https://www.cdc.gov/vaccines/acip/acip-scdm-faqs.html§ Acute respiratory illness was defined as one including any of the following signs and symptoms: fever, cough, shortness of breath, new or worsening findings on chest imaging consistent with pneumonia, or hypoxemia (defined as SpO2 <92% on room air or supplemental oxygen to maintain SpO2 ≥92%).For patients receiving chronic oxygen therapy, hypoxemia was defined as SpO2 below baseline or an escalation in supplemental oxygen use to maintain a baseline SpO2.¶ https://www.cdc.gov/flu/vaccines-work/ivy.htm by reverse transcription-polymerase chain reaction for RSV, SARS-CoV-2, and influenza.Patients who received a positive RSV, SARS-CoV-2 or influenza result based on either hospital or central laboratory testing within 10 days of illness onset or within 3 days of hospital admission were included.
Severity of RSV disease was compared with COVID-19 and influenza severity using the following in-hospital outcomes: 1) standard flow oxygen therapy, defined as receipt of supplemental oxygen at <30 L/minute; 2) receipt of high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV); 3) intensive care unit (ICU) admission; and 4) receipt of invasive mechanical ventilation (IMV) or death.For this analysis, enrolled patients were excluded if they had confirmed or inconclusive laboratory test results indicating coinfection with RSV, SARS-CoV-2, or influenza or if data for in-hospital outcomes were missing.
In-hospital outcomes were compared among patients hospitalized with RSV disease, COVID-19, and influenza using multivariable logistic regression.Models were adjusted for age, sex, self-reported race and Hispanic or Latino (Hispanic) ethnicity, number of organ systems associated with a chronic medical condition, and U.S. Department of Health and Human Services geographic region.Differences among respiratory viruses were assessed for each outcome; p-values <0.05 were considered statistically significant.All analyses were conducted using SAS software (version 9.4; SAS Institute).This activity was reviewed by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy.**
hospitalized with RSV or COVID-19, percentages of non-Hispanic Black or African American (Black) patients were similar (18.1% and 16.8%, respectively); however, among patients hospitalized with influenza, the percentage of Black patients was higher (188; 25.2%).Patients hospitalized with RSV had chronic medical conditions associated with a median of two organ systems, a finding similar to that for patients hospitalized with COVID-19 or influenza.Among the Abbreviations: aOR = adjusted odds ratio; HFNC = high-flow nasal cannula; ICU = intensive care unit; IMV = invasive mechanical ventilation; NIV = noninvasive ventilation; RSV = respiratory syncytial virus.* https://www.cdc.gov/flu/vaccines-work/ivy.htm† Multivariable logistic regression models were adjusted for age, sex, race and ethnicity, number of organ systems with chronic medical conditions, and U.S. Department of Health and Human Services region.§ Standard flow oxygen therapy was defined as receipt of supplemental oxygen therapy at a flow rate <30 L/minute as the highest level of oxygen support received during hospitalization.¶ HFNC or NIV was defined as patients who received either HFNC (oxygen therapy at a flow rate ≥30 L/minute) or NIV as the highest level of oxygen support received during hospitalization.2).The odds of the composite outcome of IMV or death between patients hospitalized with RSV and patients hospitalized with COVID-19 was similar (aOR 1.39; 95% CI = 0.98-1.96);however, among hospitalized adults aged ≥60 years with RSV, the odds of IMV or death were significantly higher compared with hospitalized influenza patients (aOR 2.08; 95% CI = 1.33-3.26).

Discussion
The findings from this study demonstrate that RSV is an important cause of respiratory virus-associated morbidity and mortality in older adults.In this prospective, multicenter analysis in which all enrolled older adults hospitalized in 20 U.S. states during 2022-2023 received testing for RSV, SARS-CoV-2, and influenza, RSV-associated hospitalizations The findings in this analysis are consistent with those from earlier studies that compared RSV disease severity among hospitalized adults with influenza disease (2)(3)(4).Although outcome definitions vary across studies, most demonstrate that patients hospitalized with RSV disease are more likely to be treated with supplemental oxygen, mechanical ventilation, or ICU admission than are patients hospitalized with influenza disease (2)(3)(4).
An important finding in this analysis is that older adults hospitalized with RSV were also more likely to receive standard flow oxygen therapy, HFNC or NIV, or be admitted to an ICU, compared with patients hospitalized with COVID-19.Few studies have compared RSV severity with that associated with COVID-19, and those that have were completed in 2020, before emergence of the Omicron variant and introduction of COVID-19 vaccines (4,5).Those studies demonstrated that patients hospitalized with RSV were less likely to experience ICU admission, mechanical ventilation, and in-hospital death than were patients hospitalized with COVID-19.Higher RSV severity relative to that of COVID-19 observed in this analysis is likely due to a combination of factors, including 1) reduced severity of Omicron variant sublineages circulating during the period of this analysis, 2) substantial increases in vaccine-and infection-conferred immunity against SARS-CoV-2, and 3) increases in use of antiviral treatments (6,7).
The high RSV disease severity observed among older adults in this analysis is important to guide decision-making for RSV

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784 included patients, 4,713 (81.5%) had received ≥1 dose of original (ancestral) monovalent or bivalent (ancestral and BA.4/5) COVID-19 vaccine, and 2,795 (48.3%) had received seasonal influenza vaccination.§ § In adjusted analyses comparing RSV severity with COVID-19, patients hospitalized with RSV were more likely than hospitalized COVID-19 patients or hospitalized influenza patients were to receive standard flow oxygen (adjusted odds ratio [aOR] = 2.97 [COVID-19] and 2.07 [influenza]), HFNC or NIV (aOR = 2.25 [COVID-19] and 1.99 [influenza]), or to be admitted to an ICU (aOR = 1.49[COVID-19] and 1.55 [influenza]) (Table All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest.Samuel M. Brown reports that ReddyPort pays royalties on his invention of an airway device, outside the submitted work.Jonathan D. Casey reports a travel grant from Fisher and Paykel, outside the submitted work.Steven Y. Chang reports consulting fees from PureTech Health and Kiniksa Pharmaceuticals and participation as a data safety monitoring board member for a study at University of California, Los Angeles outside the submitted work.James D. Chappell reports participating as a coinvestigator for a Merck investigator studies

of organ systems with a chronic medical condition, median (IQR) ¶
Abbreviations: HHS = U.S. Department of Health and Human Services; RSV = respiratory syncytial virus.* Hospitals by HHS region include Region 1: Baystate Medical Center (Springfield, Massachusetts), Beth Israel Deaconess Medical Center (Boston, Massachusetts), and Yale University (New Haven, Connecticut); Region 2: Montefiore Medical Center (New York, New York); Region 3: Johns Hopkins Hospital (Baltimore, Maryland); Region 4: Emory University Medical Center (Atlanta, Georgia), University of Miami Medical Center (Miami, Florida), Vanderbilt University Medical Center (Nashville, Tennessee), and Wake Forest University Baptist Medical Center (Winston-Salem, North Carolina); Region 5: Cleveland Clinic (Cleveland, Ohio), Hennepin County Medical Center (Minneapolis, Minnesota), Henry Ford Health (Detroit, Michigan); The Ohio State University Wexner Medical Center (Columbus, Ohio), and University of Michigan Hospital (Ann Arbor, Michigan); Region 6: Baylor Scott & White Medical Center (Temple, Texas) and Baylor University Medical Center (Dallas, Texas); Region 7: Barnes-Jewish Hospital (St. Louis, Missouri) and University of Iowa Hospitals (Iowa City, Iowa); Region 8: Intermountain Medical Center (Murray, Utah) and UCHealth, University of Colorado Hospital (Aurora, Colorado); Region 9: University of Arizona Medical Center (Phoenix, Arizona), Stanford University Medical Center (Stanford, California), and UCLA Medical Center (Los Angeles, California); and Region 10: Oregon Health & Science University Hospital (Portland, Oregon

TABLE 2 . In-hospital outcomes among adults aged ≥60 years hospitalized with respiratory syncytial virus, COVID-19, or influenza -Investigating Respiratory Viruses in the Acutely Ill Network, 25 hospitals,* 20 U.S. states, February 1, 2022-May 31, 2023 In-hospital outcomes No./Total no. (%)
less frequent than were COVID-19-associated and influenza-associated hospitalizations; however, clinical outcomes in patients hospitalized with RSV were worse than those among patients hospitalized with COVID-19 or influenza.Because RSV disease is less common than COVID-19 or influenza disease among hospitalized patients, clinicians might be less aware of RSV as a serious respiratory pathogen in older adults.
BioNTech] or mRNA-1273.222[Moderna]bivalent vaccine).Patients who received bivalent vaccine might have previously received 1-6 doses of the original (ancestral) monovalent vaccines.Patients were classified as having been vaccinated against influenza if they had received season-specific influenza vaccination based on the period during which they were enrolled.were